Motor nerve terminal restoration after focal destruction in young and old mice.
Regeneration of soleus motor nerve terminals after focal destruction by black widow spider venom (BWSV) or its active factor alpha-latrotoxin (LTx) was compared in young and old CBF-1 mice. The object was to determine whether previously reported delayed regeneration after nerve injury in old rodents was due to altered removal of debris, or delay or aberrancy in structural or functional restoration of the neuromuscular junction. In addition, the use of a new fluorescent technique permitted for the first time quantitation of the accuracy of early nerve terminal regeneration in mammalian muscle. Immunohistochemical and electron micrographic studies showed no age difference in destruction of terminals and removal of debris 2 days after toxin application. The indirect twitch and structural reinnervation (measured with flourescent techniques) returned to an equal extent in young and old mice beginning at 3 days after LTx treatment. BWSV (as opposed to LTx) delayed regeneration 1 day in young but not in old mice. On the first day of reinnervation, there was perisynaptic outgrowth in both young and old mice, although in the latter, there was a higher incidence of aberrant outgrowth. The relation between return of twitch strength and recovery of nerve terminal area (measured in teased zinc iodide-stained preparations) showed no age dependency. We conclude that factors cited to explain altered reactive sprouting in the aging CNS do not apply to regeneration of peripheral motor nerve terminals. However, it is possible that the aberrant regrowth observed at the neuromuscular junction in old mice will pertain to the aging CNS. Altered axonal rather than nerve terminal regeneration is the likely source of delayed peripheral nerve regeneration in old animals.
Robbins
N
N
Center for Neurosciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106.
Kuchynski
M
M
Polak
J
J
Grasso
A
A
D000375:Aging / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000187:drug effects; D001740:Black Widow Spider; D003714:Denervation; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D009411:Nerve Endings / Q000187:drug effects / Q000502:physiology*; D009416:Nerve Regeneration; D013111:Spider Venoms / Q000494:pharmacology; D013997:Time Factors
D013111:Spider Venoms; C020763:alpha-latrotoxin